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J R Stevens

Publications and source records attributed to J R Stevens.

At least 37 records · Page 2Linked to original sources
PubMed1999

The taxonomic position and evolutionary relationships of Trypanosoma rangeli.

This paper presents a re-evaluation of the taxonomic position and evolutionary relationships of Trypanosoma (Herpetosoma) rangeli based on the phylogenetic analysis of ssrRNA sequences of 64 Trypanosoma species and comparison of mini-exon sequences. All five isolates of T. rangeli grouped together in a clade containing Trypanosoma (Schizotrypanum) cruzi and a range of closely related trypanosome species from bats [Trypanosoma (Schizotrypanum) dionisii, Trypanosoma (Schizotrypanum) vespertilionis] and other South American mammals [Trypanosoma (Herpetosoma) leeuwenhoeki, Trypanosoma (Megatrypanum) minasense, Trypanosoma (Megatrypanum) conorhini] and an as yet unidentified species of trypanosome from an Australian kangaroo. Significantly T. rangeli failed to group with (a) species of subgenus Herpetosoma, other than those which are probably synonyms of T. rangeli, or (b) species transmitted via the salivarian route, although either of these outcomes would have been more consistent with the current taxonomic and biological status of T. rangeli. We propose that use of the names Herpetosoma and Megatrypanum should be discontinued, since these subgenera are clearly polyphyletic and lack evolutionary and taxonomic relevance. We hypothesise that T. rangeli and T. cruzi represent a group of mammalian trypanosomes which completed their early evolution and diversification in South America.

Animals↗
PubMed1999

The molecular evolution of trypanosomes.

The absence of a fossil record has meant that the evolution of protozoa has remained largely a matter for speculation. Recent advances in molecular biology and phylogenetic analysis, however, are allowing the 'history written in the genes' to be interpreted. Here, Jamie Stevens and Wendy Gibson review progress in reconstruction of trypanosome phylogeny based on molecular data from rRNA and protein-coding genes.

Africa↗
PubMed1999

The ancient and divergent origins of the human pathogenic trypanosomes, Trypanosoma brucei and T. cruzi.

This study presents new findings concerning the evolution of the human pathogens, Trypanosoma brucei and T. cruzi, which suggest that these parasites have divergent origins and fundamentally different patterns of evolution. Phylogenetic analysis of 18S rRNA sequences places T. brucei in a clade comprising exclusively mammalian trypanosomes of African origin, suggesting an evolutionary history confined to Africa. T. cruzi (from humans and sylvatic mammals) clusters with trypanosomes specific to Old and New World bats, T. rangeli and a trypanosome species isolated from an Australian kangaroo. The origins of parasites within this clade, other than some of those from bats, lie in South America and Australia suggesting an ancient southern super-continent origin for T. cruzi, possibly in marsupials; the only trypanosomes from this clade to have spread to the Old World are those infecting bats, doubtless by virtue of the mobility of their hosts. Viewed in the context of palaeogeographical evidence, the results date the divergence of T. brucei and T. cruzi to the mid-Cretaceous, around 100 million years before present, following the separation of Africa, South America and Euramerica. The inclusion in this study of a broad range of trypanosome species from various different hosts has allowed long phylogenetic branches to be resolved, overcoming the limitations of many previous studies. Moreover, T. brucei and the other mammalian tsetse-transmitted trypanosomes appear, from these data, to be evolving several times faster than T. cruzi and its relatives.

Animals↗
PubMed1997

Sensitization with clozapine: beyond the dopamine hypothesis.

Clozapine elicits dose-dependent myoclonic jerks in partially restrained rats and induces paroxysmal electroencephalographic changes, myoclonus, and convulsive seizures in a small but significant percentage of patients. With the hypothesis that the central excitatory effects of clozapine may relate to the unique therapeutic activity of this agent, rats were administered repeated alternate day or weekly very low dose (1 mg/kg) injections of clozapine in an attempt to induce the central excitatory effect through sensitization or kindling. Although initial administrations of this dose elicited no motor response or other behavioral change, repeated administration of the same low dose on either the alternate-day or weekly schedule caused increasing numbers of myoclonic seizure-like jerks (MJs) reaching 75-110 MJs/hour by the sixth clozapine injection. Clozapine-sensitized animals exhibited a significantly different pattern of early gene expression in two subcortical sites compared with vehicle-treated controls. These findings may have importance for the treatment of psychosis.

Animals↗
PubMed1997

Genetic diversity among Trypanosoma brucei rhodesiense isolates from Tanzania.

We compared 19 stocks of Trypanosoma brucei rhodesiense collected in 1991 and 1994 from Tanzania with representative stocks from other foci of Rhodesian sleeping sickness in Zambia, Kenya and Uganda. Stocks were characterized by isoenzyme electrophoresis, restriction fragment length polymorphisms in variant surface glycoprotein genes and random amplification of polymorphic DNA; the banding patterns obtained were coded for numerical analysis. In addition, the Tanzanian stocks were compared by pulsed field gel electrophoresis. Overall the Tanzanian stocks formed a homogeneous group and the predominant genotype isolated in 1991 was still present in the 1994 sample, although at a reduced level. The Tanzanian stocks were distinct from representative stocks from other East African foci. This observation does not support the proposal that there are northern and southern strains of T. b. rhodesiense, but is consistent with the view that T. b. rhodesiense stocks form a mosaic of different genotypes varying from focus to focus in East Africa.

Animals↗
PubMed1997

Anatomy of schizophrenia revisited.

The search for an anatomy of schizophrenia has engendered an enormous, almost indigestible mass of data. In no studies do all patients show the same deviations from control samples. No morphological or microscopic abnormality has been found that is either necessary or sufficient for the diagnosis. In contrast to epilepsy, in which a proliferation of excitatory pathways or inadequate inhibitory factors are paramount, schizophrenia may represent a genetically and age-determined elaboration of one or more inhibitory networks in response to specific physiological events (e.g., the increased neuronal activity in limbic and hypothalamic structures during the physiological events of puberty) or to brain injury or defect. Current diagnostic classifications, including the positive-negative categories, have not led to separation of the disorder into etiologically or pathologically similar subgroups. Analysis of morphological and other biological pathology by a different nosological principle, such as trajectory of the illness, and separate correlation of anatomical and other biological outliers with clinical and demographic factors may be more successful strategies than pooling and averaging results from a mixture of patients diagnosed with schizophrenia.

Brain↗
PubMed1996

Search for viral nucleic acid sequences in brain tissues of patients with schizophrenia using nested polymerase chain reaction.

BACKGROUND: We used polymerase chain reaction to search for nucleic acid sequences of several viruses in DNA and RNA extracted from brain tissues of schizophrenic and control subjects. METHODS: We extracted DNA and RNA templates from frozen brain specimens of 31 patients with schizophrenia and 23 nonschizophrenic control patients with other diseases. The extracts were subjected to polymerase chain reaction with oligonucleotide primers for 12 different viruses (cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1, human herpesvirus type 6, varicellazoster virus, measles virus, mumps virus, rubella virus, the picornavirus group, influenza A virus, human T-cell lymphotropic virus type I, and St Louis encephalitis virus), several of which have been suspected of involvement in schizophrenia. Nested primers were used to increase the sensitivity of the method. RESULTS: No amplified nucleic acid sequences encoded by the selected viral genomes were detected in extracts of any brain specimens from either schizophrenic or control patients. CONCLUSIONS: These data agree with previous studies that failed to find sequences of a number of viruses in the cerebrospinal fluid or selected areas of the brains of schizophrenic patients. Additional efforts should be undertaken to identify other known and unknown pathogens in schizophrenia, sampling more areas of the brain from subjects with a variety of clinical types of schizophrenia.

Brain↗
PubMed1996

Genetic heterogeneity in the Trypanosoma brucei gambiense genome analysed by random amplification of polymorphic DNA.

The random amplification of polymorphic DNA (RAPD) technique has the potential to produce large amounts of characterisation data very quickly and simply, using far less DNA than conventional restriction-fragment-length polymorphism (RFLP) analysis. In the present study we assessed genetic heterogeneity among 34 Trypanosoma brucei gambiense isolates from various endemic areas in Africa by the RAPD technique using 8 arbitrary primers and compared the results with those obtained previously from RFLP analysis of polymorphisms in 5 variant surface glycoprotein (VSG) genes. The isolates were compared both among themselves and with 3 T. b. non-gambiense isolates. Most of the primers produced RAPD profiles specific for T. b. gambiense, with 4 primers showing marked polymorphisms between T. b. gambiense and non-gambiense stocks. These primers also showed minor variations between the T. b. gambiense stocks, and 2 revealed differences between Cameroonian stocks. These results were comparable with those produced by RFLP analysis, where certain polymorphisms are characteristic of T. b. gambiense. Numerical analysis showed a high correlation between the RAPD and RFLP data, with genetic variation being detected at a finer level by RAPD analysis. We conclude that RAPD analysis provides a simple and accurate method for the characterisation of T. b. gambiense.

Animals↗
PubMed1996

Characterization of Trypanosoma brucei gambiense isolates using restriction fragment length polymorphisms in 5 variant surface glycoprotein genes.

Fifty-eight Type I Trypanosoma brucei gambiense (G) stocks, including 16 from 3 sleeping sickness foci in Cameroon, were compared by Restriction Fragment Length Polymorphism (RFLP) analysis with 14 T.b. brucei and T.b. rhodesiense stocks from various endemic areas of Africa. Loci examined were for 5 variant surface glycoprotein (VSG) genes: the LiTat 1.3, AnTat 11.17 and 2K genes were present as single copy genes, while the VSG 117 and U2 gene probes hybridised with a family of related genes. The RFLP data were subjected to cluster analysis to produce a dendrogram constructed from similarity coefficients. The LiTat 1.3 and AnTat 11.17 genes are considered to be characteristic of G stocks, and neither gene was found in the non-G stocks; however, the LiTat 1.3 gene was absent from 6 of the 58 G stocks, while the AnTat 11.17 gene was absent from 8. Supplementation of the LiTat 1.3 antigen in the Card Agglutination Test for Trypanosomiasis with the AnTat 11.17 antigen might thus improve performance of the test, particularly in Cameroon. The U2 VSG gene probe gave a characteristic RFLP pattern for G stocks, as did the VSG 117 gene; the latter is an isogene of AnTat 1.8 previously used extensively to characterise G stocks by other workers. The 2K gene was absent in some G stocks, while present in some non-G stocks, and was not therefore useful for characterisation of G stocks. In cluster analysis, the T.b. gambiense stocks formed a large homogeneous group, subdivided into 5 subgroups, with the non-gambiense stocks as a heterogeneous outgroup.

Animals↗
PubMed1996

Kindling with clozapine: behavioral and molecular consequences.

Clozapine is an 'atypical' neuroleptic that improves symptoms of many patients with schizophrenia whose illness is resistant to treatment with other neuroleptics. Unlike the 'typical neuroleptics (chlorpromazine, haloperidol), clozapine does not induce extrapyramidal symptoms such as Parkinsonism and tardive dyskinesia in humans or catalepsy in the rat. However, clozapine frequently causes epileptiform EEG changes and causes seizures in 3-5% of patients treated with this drug in therapeutic doses. Clozapine also induces dose dependent myoclonus in the partially restrained rat. In the experiments reported here, partially restrained rats were administered repeated alternate day or weekly low, fixed doses of clozapine (1 mg/kg). This dose initially caused no behavioral change. Following the third and subsequent administrations, the same dose elicited an increasing number of myoclonic seizure-like jerks reaching 140/h following the 15th injection in rats receiving the same low dose of clozapine on alternate days and 160/h following the 9th injection in animals that received the same dose once weekly. These effects are consistent with kindling, i.e. a progressive increase of brain excitability following repeated administration of a fixed subconvulsive dose of an excitatory agent. Clozapine kindled animals exhibited a significantly different pattern of early gene expression in ventral tegmental area, origin of the mesolimbic-mesocortical dopamine system and in the anterior thalamic nuclei, compared with saline treated controls subjected to exactly the same recording conditions. The evidence of central nervous system excitation with clozapine may be important to the unique therapeutic effect of this atypical antipsychotic in the treatment of symptoms, especially the deficit symptoms, of schizophrenia.

Animals↗
PubMed1996

Trypanosoma brucei s.l: evolution, linkage and the clonality debate.

The Index of Association (IA) has been proposed by Maynard Smith et al. (1993) as a general method for characterizing the population structures of microorganisms as either: clonal, epidemic, cryptic species or panmictic. With reference to the current debate surrounding the mode of reproduction in parasitic protozoa, this study explores (i) the suitability and limitations of the IA for characterizing populations of Trypanosoma brucei s.l., and (ii) the idea that the significance of genetic differences between populations may be better understood if the evolution, spread and temporal stability of certain parasite genotypes are also considered. Four populations of T. brucei from Côte d'Ivoire, Uganda and Zambia are analysed using the IA and a complementary test for linkage disequilibrium, test f of Tibayrenc, Kjellberg & Ayala (1990). The two populations from Uganda are characterized as epidemic, while the others appear more or less clonal; the merits of the two methods are compared. The implications of the various population classifications are discussed with reference to genotype longevity in each region; the evolution and biomedical consequences of the genetic non-homogeneity of T. brucei are reviewed.

Africa↗
PubMed1995

Clozapine and seizures.

Epileptiform EEG changes, myoclonus, and seizures are reported in some patients treated with clozapine. Although these are undesirable side effects, the excitation of specific neuronal networks by clozapine and other neuroleptics may be important for the therapeutic effect of this class of agents. In these experiments, intraperitoneal clozapine 2-16 mg/kg produced dose-related myoclonic jerks in partially restrained rats. Paroxysmal slow waves and spike activity were recorded from implanted electrodes in amygdala, hippocampus, and cortex following higher doses of clozapine, but the EEG abnormalities were not correlated with the myoclonic jerks. Single doses of chlorpromazine (8 and 16 mg/kg) rarely produced myoclonic jerks but provoked generalized tonic seizures in two animals preceded by multiple myoclonic jerks in one. Myoclonus and seizures reflect increased excitability of the central nervous system. It is possible that clozapine and other neuroleptics exert a therapeutic effect by increasing excitability in critical subcortical areas of the brain.

Amygdala↗
PubMed1995

Detection of linkage disequilibrium in Trypanosoma brucei isolated from tsetse flies and characterized by RAPD analysis and isoenzymes.

This study analyses the different populations of Trypanosoma brucei spp. which may coexist within the midgut of wild tsetse flies (Stevens et al. 1994). Cloned trypanosome populations characterized by multilocus enzyme electrophoresis (MLEE) were further analysed by the random amplified polymorphic DNA (RAPD) technique, allowing detection of genetic variation at a finer level than that possible by MLEE. Genetic distance matrices derived from the results of each of the two biochemical methods were calculated and compared using a computer program based on the method of Mantel (1967). The observed correlation was used to investigate the degree of linkage disequilibrium (LD) in the data, association between unrelated polymorphic markers providing a measure of the departure from panmixia. The potential of each biochemical method to detect linkage was evaluated by an extended Mantel test. The MLEE/RAPD correlation test evidenced significant LD within the population, suggesting a predominantly clonal method of reproduction for these West African trypanosomes. Analysis of RAPD data by the extended Mantel test also showed significant LD, while the results with MLEE data were less conclusive, providing an indication of the relative potential of the two techniques to detect fine genetic variation.

Animals↗